Martin, FranzAndreu, EtelvinaRovira, Juan ManuelPertusa, Jose A. G.Raurell, MercèRipoll, CristinaSanchez-Andres, Juan VicenteMontanya Mias, EduardSoria, Bernat2019-06-132019-06-131999-100012-1797https://hdl.handle.net/2445/135008Increased beta-cell sensitivity to glucose precedes the loss of glucose-induced insulin secretion in diabetic animals. Changes at the level of beta-cell glucose sensor have been described in these situations, but it is not clear whether they fully account for the increased insulin secretion. Using a euglycemic-normolipidemic 60% pancreatectomized (60%-Px) mouse model, we have studied the ionic mechanisms responsible for increased beta-cell glucose sensitivity. Two weeks after Px (Px14 group), Px mice maintained normoglycemia with a reduced beta-cell mass (0.88 +/- 0.18 mg) compared with control mice (1.41 +/- 0.21 mg). At this stage, the dose-response curve for glucose-induced insulin release showed a significant displacement to the left (P < 0.001). Islets from the Px14 group showed oscillatory electrical activity and cytosolic Ca2+ ([Ca2+]i) oscillations in response to glucose concentrations of 5.6 mmol/l compared with islets from the control group at 11.1 mmol/l. All the above changes were fully reversible both in vitro (after 48-h culture of islets from the Px14 group) and in vivo (after regeneration of beta-cell mass in islets studied 60 days after Px). No significant differences in the input resistance and ATP inhibition of ATP-sensitive K+ (K(ATP)) channels were found between beta-cells from the Px14 and control groups. The dose-response curve for glucose-induced MTT (C,N-diphenyl-N''-4,5-dimethyl thiazol 2 yl tetrazolium bromide) reduction showed a significant displacement to the left in islets from the Px14 group (P < 0.001). These results indicate that increased glucose sensitivity in terms of insulin secretion and Ca2+ signaling was not due to intrinsic modifications of K(ATP) channel properties, and suggest that the changes are most likely to be found in the glucose metabolism.8 p.application/pdfengcc-by-nc-nd (c) American Diabetes Association, 1999http://creativecommons.org/licenses/by-nc-nd/3.0/esGlucosaFisiologiaIllots de LangerhansRatolins (Animals de laboratori)Cèl·lules BGlucosePhysiologyIslands of LangerhansMice (Laboratory animals)B cellsinfo:eu-repo/semantics/article5372552019-06-13info:eu-repo/semantics/openAccess10512359